We have recently found that 17 beta-estradiol acutely improves forearm endothelium-dependent vasodilation in postmenopausal women. To determine if estrogen enhances coronary endothelium-dependent vasodilation, we studied 20 postmenopausal women, average age 61 years, 13 of whom had no significant coronary artery disease. Infusion of acetylcholine into the left main coronary artery was used to test endothelium-dependent function and infusions of nitroprusside and adenosine were used to test endothelium-independent function. Blood flow was derived from Doppler flow velocity and coronary diameter measurements. Acetylcholine, nitroprusside and adenosine were re-infused after 15 minutes of intracoronary 17 beta-estradiol at 75 ng/min. Coronary sinus estradiol levels increased from 16plus/minus11 to 282plus/minus121 pg/ml. Estradiol did not affect basal coronary flow or vascular resistance. The infusion of estradiol resulted in a 75% potentiation in the vasodilator response to acetylcholine but had no impact on nitroprusside or adenosine-induced vasodilation. Thus, 17 beta-estradiol acutely and selectively potentiates endothelium-dependent vasodilation in the coronary vasculature of postmenopausal women, an effect which may contribute to the reduction in coronary events observed with estrogen replacement therapy.